COL25A1

collagen type XXV alpha 1 chain, the group of Collagens

Basic information

Region (hg38): 4:108808725-109302752

Links

ENSG00000188517

∙ NCBI:84570 ∙ OMIM:610004 ∙ HGNC:18603 ∙ Uniprot:Q9BXS0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

fibrosis of extraocular muscles, congenital, 5 (Strong), mode of inheritance: AR
fibrosis of extraocular muscles, congenital, 5 (Moderate), mode of inheritance: AR
fibrosis of extraocular muscles, congenital, 5 (Moderate), mode of inheritance: AR
ptosis, hereditary congenital, 1 (Supportive), mode of inheritance: AD
fibrosis of extraocular muscles, congenital, 5 (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Fibrosis of extraocular muscles, congenital 5	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal	25500261

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the COL25A1 gene.

Inborn_genetic_diseases (72 variants)
not_provided (30 variants)
COL25A1-related_disorder (14 variants)
Fibrosis_of_extraocular_muscles,_congenital,_5 (10 variants)
Arthrogryposis (1 variants)
Arthrogryposis_multiplex_congenita (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the COL25A1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000198721.4. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous				17 clinvar	4 clinvar	21
missense	1 clinvar	1 clinvar	76 clinvar	4 clinvar	1 clinvar	83
nonsense	2 clinvar	1 clinvar				3
start loss						0
frameshift	1 clinvar					1
splice donor/acceptor (+/-2bp)		2 clinvar				2
Total	4	4	76	21	5

Highest pathogenic variant AF is 0.00000684338

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
COL25A1	protein_coding	protein_coding	ENST00000399132	36	491937

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.64e-18	0.894	124729	0	70	124799	0.000280

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.45	301	381	0.791	0.0000196	4101
Missense in Polyphen		88	134.52	0.65416		1382
Synonymous	0.0380	126	127	0.996	0.00000677	1346
Loss of Function	2.30	37	55.5	0.667	0.00000270	668

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000504	0.000503
Ashkenazi Jewish	0.00	0.00
East Asian	0.000168	0.000167
Finnish	0.000186	0.000186
European (Non-Finnish)	0.000322	0.000318
Middle Eastern	0.000168	0.000167
South Asian	0.000499	0.000490
Other	0.000333	0.000330

dbNSFP

Source: dbNSFP

Function: FUNCTION: Inhibits fibrillization of amyloid-beta peptide during the elongation phase. Has also been shown to assemble amyloid fibrils into protease-resistant aggregates. Binds heparin. {ECO:0000269|PubMed:15522881, ECO:0000269|PubMed:15615705, ECO:0000269|PubMed:15853808, ECO:0000269|PubMed:16300410}.;
Disease: DISEASE: Fibrosis of extraocular muscles, congenital, 5 (CFEOM5) [MIM:616219]: An ocular motility disorder characterized by congenital dysinnervation of various cranial nerves to ocular muscles. Clinical features are ophthalmoplegia, anchoring of the eyes in downward gaze, ptosis, and backward tilt of the head. {ECO:0000269|PubMed:25500261}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Collagen chain trimerization;Collagen biosynthesis and modifying enzymes;Collagen degradation;Collagen formation;Extracellular matrix organization;Degradation of the extracellular matrix (Consensus)

Recessive Scores

pRec: 0.105

Intolerance Scores

loftool: 0.164
rvis_EVS: -0.36
rvis_percentile_EVS: 29.31

Haploinsufficiency Scores

pHI: 0.151
hipred: Y
hipred_score: 0.613
ghis: 0.454

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.468

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Col25a1
Phenotype: cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype;

Gene ontology

Biological process: extracellular matrix organization;axonogenesis involved in innervation
Cellular component: extracellular region;collagen trimer;extracellular space;endoplasmic reticulum lumen;plasma membrane;integral component of plasma membrane;integral component of membrane;extracellular matrix
Molecular function: amyloid-beta binding;extracellular matrix structural constituent;heparin binding